Project 4: "Directional Diffusivity as a Window into the Pathology of MS"1'3*7 As a direct translation of Project 1, Project 4 is a MRI centered study. It has become clear that the pathologies observed in MS patient CMS are varied. Conventional clinical MRI lacks specificity for these pathologies. The hypothesis to be tested is that the pathology of lesions in MS and related diseases can be identified in vivo within white matter tracts using directional diffusivities derived from DTI. The feasibility of using directional diffusivities obtained by DTI to discern pathology in the white matter tracts of brains and spinal cords of living humans will be determined. Project 4 will determine the ability of DTI to predict the evolution of acute gadolinium (Gd)-enhancing MS lesions into T1 hypointensities ("black holes") over 1 year, determine whether A,|| and A,j_ can differentiate poor vs. good functional outcomes in MS patients with remote and stable cervical spinal cord (SC) lesions, prospectively examine patients with acute cervical transverse myelitis (TM) using DTI and to correlate the results with eventual recovery, and verify that axonal injury/loss is the substrate for changes in XH and that demyelination is the substrate for increased A.J. in human spinal cord using post-mortem CMS specimens (existing data).